miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and irinotecan.

INTRODUCTION: MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. METHODS: From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood using the TaqMan MicroRNA Array v2.0. Mutation status of KRAS, BRAF, and PI3KCA was known. RESULTS: After Bonferroni adjustment, 6 miRNAs: (miR-345, miR-143, miR-34a*, miR-628-5p, miR-886-3p and miR-324-3p), were found associated with short OS. miR-345 was the strongest prognostic miRNA, significant in the full cohort and in the non-KRAS mutant population. miR-345, as a continuous variable in the full cohort, resulted in a hazard ratio (HR) of 2.38 per IQR (CI 95%: 1.8-3.1, P-value = 2.86e-07, Bonferroni adjusted, univariable analysis) and a HR = 1.75 per IQR (CI 95%: 1.24-2.48, P-Wald = 1.45e-03) in the multivariable analysis adjusted for gender, age, KRAS, PI3KCA and performance status. miR-345 was prognostic in progression-free survival (PFS) with a HR = 1.63 per IQR (CI 95%: 1.25-2.114, P-Wald = 2.92e-4) in the multivariable analysis. In addition, high miR-345 expression was associated with lack of response to treatment with cetuximab and irinotecan. CONCLUSION: We identified miR-345 in whole blood as a potential biomarker for clinical outcome. MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and also in the non-KRAS mutant population

Access and metro network convergence for flexible end-to-end network design

This paper reports on the architectural, protocol, physical layer, and integrated testbed demonstrations carried out by the DISCUS FP7 consortium in the area of access - metro network convergence. Our architecture modeling results show the vast potential for cost and power savings that node consolidation can bring. The architecture, however, also recognizes the limits of long-reach transmission for low-latency 5G services and proposes ways to address such shortcomings in future projects. The testbed results, which have been conducted end-to-end, across access - metro and core, and have targeted all the layers of the network from the application down to the physical layer, show the practical feasibility of the concepts proposed in the project

Manifestation of Resonance-Related Chaos in Coupled Josephson Junctions

Chaotic features of systems of coupled Josephson junctions are studied. Manifestation of chaos in the temporal dependence of the electric charge, related to a parametric resonance, is demonstrated through the calculation of the maximal Lyapunov exponent, phase-charge and charge-charge Lissajous diagrams and correlation functions. The number of junctions in the stack strongly influences the fine structure in the current voltage characteristics and a strong proximity effect results from the nonperiodic boundary conditions. The observed resonance-related chaos exhibits intermittency over a range of conditions and parameters. General features of the system are analyzed by means of a linearized equation and the criteria for a breakpoint region with no chaos are obtained. Such criteria could clarify recent experimental observations of variations in the power output from intrinsic Josephson junctions in high temperature superconductors.Comment: 13 pages, 16 figure

Overcoming High Energy Backgrounds at Pulsed Spallation Sources

Instrument backgrounds at neutron scattering facilities directly affect the quality and the efficiency of the scientific measurements that users perform. Part of the background at pulsed spallation neutron sources is caused by, and time-correlated with, the emission of high energy particles when the proton beam strikes the spallation target. This prompt pulse ultimately produces a signal, which can be highly problematic for a subset of instruments and measurements due to the time-correlated properties, and different to that from reactor sources. Measurements of this background have been made at both SNS (ORNL, Oak Ridge, TN, USA) and SINQ (PSI, Villigen, Switzerland). The background levels were generally found to be low compared to natural background. However, very low intensities of high-energy particles have been found to be detrimental to instrument performance in some conditions. Given that instrument performance is typically characterised by S/N, improvements in backgrounds can both improve instrument performance whilst at the same time delivering significant cost savings. A systematic holistic approach is suggested in this contribution to increase the effectiveness of this. Instrument performance should subsequently benefit.Comment: 12 pages, 8 figures. Proceedings of ICANS XXI (International Collaboration on Advanced Neutron Sources), Mito, Japan. 201

Ultrasound measurement of joint cartilage thickness in large and small joints in healthy children: a clinical pilot study assessing observer variability

<p>Abstract</p> <p>Background</p> <p>Loss of joint cartilage is a feature of destructive disease in JIA. The cartilage of most joints can be visualized with ultrasonography (US). Our present study focuses on discriminant validity of US in children. We studied reproducibility between and within a skilled and a non-skilled investigator of US assessment of cartilage thickness in small and large joints in healthy children.</p> <p>Methods and results</p> <p>In 11 healthy children (5 girls/6 boys), aged 9.6 years (9.3–10 years), 110 joints were examined. Cartilage thickness of the right and left hip, knee, ankle, 2^ndmetacarpophalangeal (MCP), and 2^ndproximal interphalangeal (PIP) joint independently. The joints were examined twice, two days apart by a skilled and a non-skilled investigator. Mean cartilage thickness in the five joints was: hip 2.59 ± 0.41, knee 3.67 ± 0.64, ankle 1.08 ± 0.31, MCP 1.52 ± 0.27 and PIP 0.73 ± 0.15 mm. We found the same mean differences in CTh of 0.6 mm in the inter-observer part with regard of the PIP joint. Within investigators (intra-observer), the smallest mean difference of CTh was found in the MCP joint with -0.004 (skilled) and 0.013 mm (non-skilled).</p> <p>Conclusion</p> <p>We found the level of agreement between observers within a 95% Confidence Interval in assessment of cartilage thickness in hip-, knee-, ankle-, MCP-, and PIP joints in healthy children. Observer variability seems not to relate to joint size but to the positioning of the joints and the transducer. These factors seem to be of major importance for reproducible US measurements. The smallest difference in measurement of cartilage thickness <it>between observers </it>was found in the PIP joint, and <it>within observers </it>in the MCP joint and it seems that using EULAR standard US guidelines is feasible for a pediatric setting. The use of US in children is promising. Studies on larger groups of children are needed to confirm the validation and variability of US in children as well as determining the smallest detectable difference of US measures.</p

Beta decay of r-process waiting-point nuclei in a self-consistent approach

Beta-decay rates for spherical neutron-rich r-process waiting-point nuclei are calculated within a fully self-consistent Quasiparticle Random-Phase Approximation, formulated in the Hartree-Fock-Bogolyubov canonical single-particle basis. The same Skyrme force is used everywhere in the calculation except in the proton-neutron particle-particle channel, where a finite-range force is consistently employed. In all but the heaviest nuclei, the resulting half-lives are usually shorter by factors of 2 to 5 than those of calculations that ignore the proton-neutron particle-particle interaction. The shorter half-lives alter predictions for the abundance distribution of r-process elements and for the time it takes to synthesize them.Comment: 14 pages RevTex, 10 eps figures, submitted to Phys. Rev.

Tailored preconceptional dietary and lifestyle counselling in a tertiary outpatient clinic in the Netherlands

Background Adverse reproductive performance has been linked to unhealthy dietary intake and lifestyles. Our objectives were to investigate the prevalence of unhealthy dietary intake and lifestyles before conception and to evaluate whether tailored preconception counselling modifies these behaviours. Methods Between October 2007 and April 2009, 419 couples received tailored preconception dietary and lifestyle counselling at the outpatient clinic of Obstetrics and Gynaecology of the Erasmus University Medical Center Rotterdam, the Netherlands. A subgroup (n = 110 couples) was counselled twice with a fixed time interval of 3 months. Self-administered questionnaires were used for tailored dietary and lifestyle counselling. A cumulative score based on six Dutch dietary guidelines was displayed in the personal Preconception Dietary Risk score (PDR score). In a similar manner, the Rotterdam Reproduction Risk score (R3 score) was calculated from lifestyle factors (women: 13 items, men: 10 items). Univariate and paired tests were used. Results Most couples (93.8) were subfertile. At the second counselling, the percentage consuming the recommended intake of fruit had increased from 65 to 80 in women and from 49 to 68 in men and the percentage of women getting the recommended intake of fish increased from 39 to 52. As a consequence, the median PDR score was decreased [women: 2.6 (95 CI 2.4-2.9) to 2.4 (95 CI 2.1-2.6), men: 2.5 (95 CI 2.3-2.7) to 2.2 (95 CI 1.9-2.4), both P < 0.05]. The median R3 scores were also lower [women: 4.7 (95 CI 4.3-5.0) to 3.1 (95 CI 2.8-3.4), men: 3.0 (95 CI 2.8-3.3) to 2.0 (95 CI 1.7-2.3), both P < 0.01] due to less alcohol use (-14.6), more physical exercise and folic acid use in women, and less alcohol use in men (-19.4) (all P < 0.01). The R3 scores in women and men were decreased in all ethnicity, educational level, neighbourhood and BMI categories. However, low educated women appeared to show a larger reduction than better educated women and men with a normal BMI to show a larger decrease than overweight men. The reduction in the PDR score of women was similar in both ethnic groups. More than 85 women and men found the counselling useful and around 70 would recommend it to others. Conclusions Tailored preconception counselling about unhealthy dietary and lifestyle behaviours of subfertile couples in an outpatient tertiary clinic is feasible and seems to decrease the prevalence of harmful behaviours in the short term. These Results with subfertile couples are promising and illustrate their opportunities to contribute to reproductive performance and pregnancy outcome